One of the most peculiar characteristics of the major histocompatibility complex (MHC) is its polymorphism. While virtually all other genetic loci occur in natural populations in no more than three or four forms (alleles), a large number of alleles has been suspected to occur at the MHC loci of the various mammalian species, including man and mouse. The goal of the proposed project is to determine the extent of the H-2 complex, which represents the MHC of the mouse. The problem is approached in two ways: First, H-2 haplotypes are extracted from wild mice and placed on an inbred background of strain C57BLMOSn (equals B10), thus producing a series of B10.W lines, which can then be used for detailed study of wild-derived H-2 haplotypes and for production of specific antibodies to wild-derived H-2 antigens. Second, wild mice trapped in different localities and different geographic areas are typed directly with specific anti-H-2 reagents. As a control, loci linked to the H-2 complex are also studied. The aims of the project are to determine frequencies of alleles at individual H-2 loci, number of alleles existing in a given population, degree of heterozygosity, variations in allelic frequencies caused by selection, and identification of some of the selective forces. It is hoped that by elucidating the H-2 polymorphism we shall learn a great deal also about the HLA polymorphism, and in particular about the reasons for the association between certain HLA antigens and diseases.